DESCRIPTION (provided by candidate): The binding of growth hormone (GH) to GH receptor (GHR) activates JAK2, which phosphorylates itself, GHR, and induces the activation of signaling pathways. JAK2 is required for the majority of GH-induced cellular activities. However, all proteins currently known to interact directly with JAK2 are regulatory in nature. I propose that JAK2 also interacts directly with signaling molecules. This lab has recently identified a number of autophosphorylation sites within JAK2. Since phosphorylated tyrosines are prime targets for the binding of signaling molecules with SH2 or PTB domains, phosphopeptides will be used to screen for JAK2 interacting proteins using the COLT assay. Any clones developed from this will then be verified in vivo and investigated for functional consequence of JAK2 interaction. These studies will provide insight into new GH signaling proteins, new GH signaling pathways, and potentially new cellular responses to GH that are responsible for the diverse actions of GH on body growth and metabolism. JAK2-signaling protein interactions identified may also provide insight into signaling pathways and cellular responses of the many other cytokine receptors that activate JAK2.